On October 18, 2025 Astrazeneca reported positive results from the DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) in patients with a high risk of disease recurrence. The trial compared Enhertu with trastuzumab emtansine (T-DM1) as a post-neoadjuvant treatment (after surgery) in patients with HER2-positive early breast cancer with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results showed Enhertu significantly reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1 as a post-neoadjuvant treatment (based on an IDFS hazard ratio [HR] of 0.47, 95% confidence interval [CI] 0.34-0.66, p<0.0001). At three years, 92.4% of patients in the Enhertu arm were alive and free of invasive disease, compared with 83.7% of those in the T-DM1 arm. The IDFS results were consistent across all prespecified subgroups.

Enhertu also significantly reduced the risk of disease recurrence or death (disease-free survival [DFS]), a key secondary endpoint, by 53% (HR 0.47; 95% CI 0.34-0.66; p<0.0001). Further, Enhertu lowered the risk of distant disease recurrence (distant recurrence-free interval [DRFI]) by 51% and the risk of brain metastases (brain metastasis-free interval [BMFI]) by 36% versus T-DM1.

Overall survival (OS) was not mature at the time of this planned interim analysis (2.9% maturity at data cut-off) and will be assessed in future analyses (HR 0.61; 95% CI 0.34-1.10).

Charles Geyer, MD, Chief Scientific Officer of the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP) Foundation, Professor of Medicine at the UPMC Hillman Cancer Center and principal investigator for the trial, said: "For patients with residual disease after neoadjuvant treatment, the post‑neoadjuvant setting represents a critical second opportunity to reduce recurrence risk, and in DESTINY‑Breast05 Enhertu reduced the risk of early recurrence or death by 53 per cent compared to the current standard of T‑DM1. These results, coupled with the safety data from the trial, are likely to transform clinical practice in the post-neoadjuvant setting for patients with high-risk disease, with the potential for Enhertu to set a new standard of care."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Progress in treating HER2-positive early breast cancer has been significant, yet managing patients at a higher-risk of recurrence remains challenging. These landmark data, alongside those from DESTINY-Breast11, underscore the potential of Enhertu to become a foundational treatment in early-stage breast cancer, increasing the likelihood that more patients could be cured in this setting."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The results of DESTINY-Breast05 demonstrate a clear benefit of Enhertu over the current standard of care in patients with high-risk HER2-positive early breast cancer following surgery, improving their chance for sustained long-term outcomes. These results, coupled with the results of DESTINY-Breast11, illustrate the continued promise of Enhertu to move earlier in the breast cancer treatment paradigm where it can have the greatest impact on the lives of patients."

Summary of Results: DESTINY-Breast05i

Efficacy Measure

Enhertu
(5.4 mg/kg; n=818)

T-DM1
(n=817)

IDFSii

3-year IDFS rate, %

92.4

83.7

HR 0.47 (95% CI 0.34-0.66); p<0.0001

DFSiii

3-year DFS rate, %

92.3

83.5

HR 0.47 (95% CI 0.34-0.66); p<0.0001

DRFIiv

3-year event-free rate, %

93.9

86.1

HR 0.49 (95% CI 0.34-0.71)

BMFIv

3-year event-free rate, %

97.6

95.8

HR 0.64 (95% CI 0.35-1.17)

OSvi

Survival at 3 years, %

97.4

95.7

HR 0.61 (95% CI 0.34-1.10)

TDM-1, trastuzumab emtansine; CI, confidence interval; HR, hazard ratio; IDFS, invasive disease-free survival; DFS, disease-free survival; DRFI, distant recurrence-free interval; BMFI, brain-metastasis-free interval; OS, overall survival

i Data cut-off 2 July 2025
ii IDFS is defined as the time from randomisation until the date of first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumour, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence or death from any cause; based on investigator assessment; statistically evaluated using the pre-specified hierarchical testing procedure
iii DFS is defined as the time between randomisation and the date of the first occurrence of an IDFS event per STEEP criteria, including second primary non-breast cancer event, or contralateral or ipsilateral ductal carcinoma in situ (DCIS); based on investigator assessment; statistically evaluated using the pre-specified hierarchical testing procedure
iv DRFI is defined as the time between randomisation and the date of distant breast cancer recurrence; based on investigator assessment
v BMFI is defined as the time between randomisation and the date of documentation of brain metastases or leptomeningeal disease; based on investigator assessment
vi 2.9% maturity

The safety profile of Enhertu observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified. Grade 3 or higher treatment emergent adverse events (AEs) rates were comparable between Enhertu and T-DM1 (50.6% versus 51.9%). Rates of interstitial lung disease (ILD) were low in both arms with ILD events occurring in 9.6% of the Enhertu arm and 1.6% of the T-DM1 arm. The majority of ILD events were low Grade (Grade 1 or 2). There were no Grade 3 or higher ILD events for T-DMI. There were seven Grade 3 events and no Grade 4 events in the Enhertu arm. There were two Grade 5 events in the Enhertu arm as determined by an independent adjudication committee.

The DESTINY-Breast05 results (abstract #LBA1) will be presented today during Presidential Symposium I alongside the results of the DESTINY-Breast11 Phase III trial (abstract #291O) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Congress in Berlin, Germany.

DESTINY-Breast05 was conducted in collaboration with the NSABP, the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast Cancer Research Group.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Notes

Post neoadjuvant treatment for HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer are considered HER2-positive.3

For patients with HER2-positive early breast cancer, achieving pCR with neoadjuvant treatment is the earliest indicator of improved long-term survival.4 However, approximately half of patients who receive neoadjuvant treatment do not reach pCR and have poorer long-term outcomes, putting them at increased risk of disease recurrence.5-9

Post-neoadjuvant therapy represents a key opportunity to minimise the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. Despite receiving additional treatment with T-DMI in the post-neoadjuvant setting, approximately 20% of patients still experience invasive disease or death and no reduction in the risk of CNS recurrence.10,11 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%.12

New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.

DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2-positive early breast cancer with residual invasive disease in breast and/or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.

The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS. IDFS is defined as the time from randomisation until first recurrence, distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include OS, distant recurrence-free interval, brain metastases-free interval and safety.

DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2-monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridisation (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer.

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

(Press release, AstraZeneca, OCT 18, 2025, View Source [SID1234656784])

On October 18, 2025 Astrazeneca reported positive results from the DESTINY-Breast11 Phase III trial showed Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) in the neoadjuvant setting (before surgery) demonstrated a statistically significant and clinically meaningful improvement in the pathologic complete response (pCR) rate. The trial compared Enhertu followed by THP with dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer. Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In DESTINY-Breast11, Enhertu followed by THP resulted in a pCR rate of 67.3% compared with 56.3% for ddAC-THP, representing a pCR rate improvement of 11.2%. Improvement in pCR rates was observed across both hormone receptor (HR)-positive and HR-negative subgroups (HR-positive: 61.4% versus 52.3%; HR-negative: 83.1% versus 67.1%). Additionally, after surgery, 81.3% of patients who received neoadjuvant treatment in the Enhertu followed by THP arm had no or minimal residual invasive cancer (residual cancer burden [RCB] 0+I) detected in the resected breast or lymph node tissue compared to 69.1% of patients in the comparator arm.

The secondary endpoint of event-free survival (EFS) was not mature at the time of this analysis (4.5% maturity at data cutoff); however, an early analysis showed a trend favouring Enhertu followed by THP versus ddAC-THP (hazard ratio 0.56; 95% CI 0.26-1.17).

Nadia Harbeck, MD, PhD, Director of Breast Center, Cancer Department of OB&GYN and CCC Munich, LMU University Hospital, Germany and principal investigator for the trial, said: "For patients with early breast cancer who are at high risk of disease recurrence, using the most effective treatment option at the earliest opportunity is critical to prevent recurrence, optimise safety and improve the potential for cure. In the DESTINY-Breast11 trial, more than two thirds of patients had a pathologic complete response with trastuzumab deruxtecan followed by THP, suggesting a potential new standard of care in the neoadjuvant setting for patients with high-risk, HER2-positive early breast cancer."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The goal of treatment in the early breast cancer setting is to provide patients with the best possible chance for cure whilst optimising the tolerability of the treatment regimen. The impressive pathologic response rates and favourable safety profile seen with Enhertu followed by THP in DESTINY-Breast11 have the potential to transform treatment in the neoadjuvant setting and underscore the importance of bringing Enhertu into earlier stages of HER2-positive disease."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "While achieving a pathologic complete response in HER2-positive early-stage breast cancer is critical for reducing disease recurrence and improving long-term prognosis, approximately half of patients still show evidence of residual disease following surgery with currently available neoadjuvant treatment options. The results from DESTINY-Breast11 show that treatment with Enhertu followed by THP prior to surgery resulted in no evidence of residual invasive disease in two thirds of patients, illustrating the first treatment regimen in more than a decade to significantly improve outcomes in the earliest treatment setting for HER2-positive breast cancer."

Summary of Results: DESTINY-Breast11i,ii

Efficacy Measure

Enhertu (5.4 mg/kg; 4 cycles) followed by THP (4 cycles) (n=321)

ddAC (4 cycles) followed by THP (4 cycles)
(n=320)

pCR

pCR rate, %iii

67.3

56.3

ΔpCR,% (95% CI)iii,iv

11.2 (4.0-18.3)

p=0.003

HR-positive subgroup pCR rate, %iii

61.4

52.3

ΔpCR, % (95% CI)

9.1 (0.2-17.9)

HR-negative subgroup pCR rate, % iii

83.1

67.1

ΔpCR, % (95% CI)

16.1 (3.0-28.8)

RCB (0+I)v

RCB (0+I rate), %

81.3

69.1

ΔRCB, %

12.2

RCB-I rate, %

68.8

57.5

RCB-0 rate, %

12.5

11.6

HR-positive subgroup RCB (0+I) rate, %

78.0

64.7

ΔRCB, % (95% CI)

13.3

HR-positive RCB-I rate, %

63.1

52.8

HR-positive RCB-0 rate, %

14.8

11.9

HR-negative subgroup RCB (0+I) rate, %v

90.4

81.2

ΔpCR, % (95% CI)

9.2

HR-negative RCB-I rate, %

84.3

70.6

HR-negative RCB-0 rate, %

6.0

10.6

EFSvi

2-year EFS, %

Hazard ratio (95% CI)

96.9

93.1

0.56 (0.26, 1.17)

THP, paclitaxel, trastuzumab and pertuzumab; ddAC, dose-dense doxorubicin and cyclophosphamide; pCR, pathologic complete response; HR, hormone receptor; CI, confidence interval; RCB (0+I), residual cancer burden; EFS, event-free survival

i Data cut-off 12 March 2025; median duration of follow up was 24.2 months with Enhertu followed by THP and 23.6 months with ddAC-THP
ii Based on blinded central review
iii pCR responders were defined as patients who only received randomised study treatment (at least one dose) and had pCR
iv Stratified Miettinen & Nurminen method; p value crossed the 0.03 prespecified boundary
v RCB is based on raw data and is not corrected for non-starters, or any bridging/off study neoadjuvant treatment; therefore, there may be differences between pCR and RCB-0
vi EFS was 4.5% mature at interim analysis

The safety profile of Enhertu followed by THP in DESTINY-Breast11 was consistent with the known profiles of each individual therapy with no new safety concerns identified.

Enhertu followed by THP showed a favourable safety profile compared with ddAC-THP with reduced rates of Grade 3 or higher adverse events (AEs) (37.5% versus 55.8%), serious AEs (10.6% versus 20.2%), treatment interruptions (37.8% versus 54.5%) and left ventricular dysfunction (1.3% versus 6.1%).

Rates of interstitial lung disease (ILD) were low and similar between arms with ILD events occurring in 4.4% of patients in the Enhertu followed by THP arm compared with 5.1% in the ddAC-THP arm. The majority of ILD events were low Grade (Grade 1 and 2). There was one Grade 3/4 event in the Enhertu followed by THP arm and five Grade 3/4 events in the ddAC-THP arm. There was one Grade 5 ILD event in each arm as determined by an independent adjudication committee.

DESTINY-Breast11 results (abstract #291O) will be presented today during Presidential Symposium I, alongside the results from the DESTINY-Breast05 Phase III trial (abstract #LBA1) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Congress in Berlin, Germany. The DESTINY-Breast11 results will also be published in the Annals of Oncology in parallel with ESMO (Free ESMO Whitepaper).

A supplemental Biologics License Application for Enhertu followed by THP based on the results from DESTINY-Breast11 is currently under review by the US Food and Drug Administration (FDA).

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by Daiichi Sankyo and AstraZeneca.

Notes

HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer are considered HER2-positive.3

Approximately one in three patients with HER2-positive early breast cancer are considered high-risk, meaning they are more likely to experience disease recurrence and have a poor prognosis.4 For patients with HER2-positive early breast cancer, achieving pCR with neoadjuvant treatment is the earliest indicator of improved long-term survival.5 However, approximately half of patients who receive neoadjuvant treatment do not reach pCR.6-10

The current standard of care in the HER2-positive neoadjuvant setting in many regions of the world consists of combination chemotherapy regimens.11 These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiotoxicity, reinforcing the need for new treatment options.11-13

DESTINY-Breast11
DESTINY-Breast11 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of neoadjuvant Enhertu (5.4 mg/kg) monotherapy or Enhertu followed by THP (paclitaxel, trastuzumab and pertuzumab) versus ddAC-THP in patients with high-risk (lymph node positive [N1-3] or primary tumour stage T3-4), locally advanced or inflammatory HER2-positive early-stage breast cancer.

Patients were randomised 1:1:1 to receive either eight cycles of Enhertu monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC followed by four cycles of THP.

The Enhertu monotherapy arm was closed early following a recommendation from the Independent Data Monitoring Committee (IDMC). The recommendation was based on multiple factors including a lower pCR rate, low likelihood that Enhertu alone would be superior to ddAC-THP, and timing of surgery. The recommendation was not related to safety.

The primary endpoint of DESTINY-Breast11 is rate of pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety.

DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer.

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

(Press release, AstraZeneca, OCT 18, 2025, View Source [SID1234656783])

On October 18, 2025 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported updated data from the Phase 1b/2 study of palazestrant in combination with ribociclib in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. These findings will be presented in a poster session on October 20 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased with these latest data showing compelling progression-free survival and favorable tolerability of palazestrant plus ribociclib, further reinforcing this regimen’s potential as a new standard of care in metastatic breast cancer," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "These data showcase the activity of the combination in both ESR1 mutant and wild-type tumors, an important component for effective frontline treatment, and underscore the importance of complete ER antagonism in the treatment of ER-positive breast cancer. As we work to transform the breast cancer treatment paradigm, we are increasingly confident in palazestrant’s potential to become a best-in-class, backbone endocrine therapy and are excited to now have our second Phase 3 trial, OPERA-02, underway evaluating palazestrant with ribociclib in the frontline setting."

Key Findings from the Phase 1b/2 Study of Palazestrant in Combination with Ribociclib
As of July 8, 2025, 72 patients were enrolled across the 90 mg and 120 mg palazestrant dose cohorts. 56 patients received 120 mg once-daily palazestrant and 16 patients received 90 mg once-daily palazestrant, all with the approved dose of ribociclib for metastatic breast cancer of 600 mg daily. 45 (63%) patients had prior treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy for advanced disease. 33% (15/45) of patients who had prior treatment with CDK4/6i in the advanced setting (2/3L) had an ESR1 mutation at baseline.

Efficacy

In the 90 mg palazestrant dose cohort, with a median follow-up of 10.8 months, median progression-free survival (PFS) was not reached.
In the 120 mg palazestrant dose cohort, with a median follow-up of more than 19 months, median PFS are mature. Median PFS was 15.5 months for all patients. Median PFS was 12.2 months for those who received prior treatment with CDK4/6i, including 9.2 months for patients with ESR1 wild-type tumors and 13.8 months for patients with tumors with ESR1 mutations.

Safety and Pharmacokinetics

Across 72 patients treated, 90 mg or 120 mg of palazestrant combined with 600 mg of ribociclib daily was well tolerated with no new safety signals or increase in toxicity.
Palazestrant and ribociclib did not demonstrate any drug-drug interactions and the overall safety profile was consistent with the established safety profile of ribociclib plus an endocrine therapy.
The majority of treatment-emergent adverse events were grade 1 or 2, and the severity and incidence of adverse events were consistent with the expected safety profile of each drug.

"Despite recent advances in the treatment of ER+/HER2- metastatic breast cancer, there remains a significant need for therapies that can overcome endocrine resistance, particularly following treatment with a CDK4/6 inhibitor," said Dr. Nancy Lin, Associate Chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, at the Dana-Farber Cancer Institute. "I am very encouraged by these new data showing the novel palazestrant-ribociclib combination compares favorably to other endocrine therapy-CDK4/6 inhibitor combinations. With a compelling median PFS in the challenging post-CDK4/6 inhibitor setting, I believe palazestrant has the potential to serve as an important combination agent in the metastatic setting."

Poster Presentation Details
Title: Palazestrant (OP-1250) plus ribociclib in patients with estrogen receptor-positive,
human epidermal growth factor receptor 2-negative (ER+, HER2-) advanced breast cancer (ABC)
Poster Number: 502P
Session: Breast Cancer, Metastatic Session
Date/Time: Monday, October 20, 2025, from 12:00-12:45pm CEST / 6:00-6:45am ET

Additional information can be found on the ESMO (Free ESMO Whitepaper) 2025 website, including abstracts. A copy of the poster will be made available on the Publications page of Olema’s website in alignment with the ESMO (Free ESMO Whitepaper) 2025 embargo policy.

(Press release, Olema Oncology, OCT 18, 2025, View Source [SID1234656776])

On October 18, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported the presentation of new clinical data from its first-in-human Phase 1a study of NX-1607, a first-in-class oral inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) in patients with relapsed/refractory solid tumors. The data are being presented at the European Society for Medical Oncology Congress (ESMO 2025), taking place October 17–21, 2025, in Berlin, Germany.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As a first-in-class oral inhibitor of CBL-B, NX-1607 may offer a novel therapeutic approach to treat solid tumors by targeting a previously unaddressed pathway in immune regulation affecting not only T cells, but also multiple immune cell types, including dendritic cells and natural killer cells, which all play critical roles in the tumor microenvironment," said Paula O’Connor, M.D., chief medical officer of Nurix. "These data highlight NX-1607’s activity as an immuno-oncology agent, showing promising signs of biologic activity and clinical benefit, and supporting its continued development as an innovative next generation checkpoint inhibitor therapy designed to improve outcomes for cancer patients."

In a poster titled: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, data were presented from a total of 82 patients with eleven different tumor types treated across six once-daily (QD) and five twice-daily (BID) dosing regimens ranging from 5 mg to 80 mg total daily dose. Patients were heavily pre-treated with a median of 3 prior regimens including a median of 1 prior chemo/immunotherapy regimen. NX-1607 demonstrated dose-dependent exposure, increases in proximal and distal biomarkers, evidence of peripheral immune activation, and reductions in tumor volume and cancer biomarkers. Despite the advanced stages of disease and the broad range of tumor types included in the trial, NX-1607 demonstrated evidence of clinical activity including reductions in tumor-specific biomarkers (prostate-specific antigen (PSA) in prostate cancer and carcinoembryonic antigen (CEA) in colorectal cancer), long-term stable disease, and a confirmed partial response in a patient with micro-satellite stable colorectal cancer (MSS CRC), a tumor type typically unresponsive to immune checkpoint therapy. As of the 26 July 2025 data cut, 71 patients were evaluable for response, with a disease control rate (DCR) of 49.3%. With respect to duration of response, 7 patients achieved either stable disease (SD) or partial response (PR) for ≥5 months on treatment and 1 patient with MSS CRC achieved a PR and was treated for 27 months. Further supporting the dose-dependent activity of NX-1607, the greatest reductions in PSA among the prostate cancer patients were achieved in the BID dosing groups with 6/13 patients having PSA reductions of ≥50%.

NX-1607 was shown to be tolerable at pharmacologically active doses and has a safety profile comparable to approved immuno-oncology agents, with most adverse events Grade 2 or less in severity. Immune-related adverse events were observed in 6 patients, indicating on-target immune activation, similar to what is observed with PD-1/PD-L1 therapies. The most common treatment emergent adverse events included nausea and vomiting, which were mitigated by both BID dosing and the introduction of a step-up dosing regimen where patients were initially treated at lower doses and increased to the target dose during the first cycle of treatment.

"NX-1607 has demonstrated potent single agent activity preclinically and now most importantly, we see clear signals of anti-tumor activity in patients with advanced disease. The results are particularly intriguing in MSS colorectal cancer and metastatic prostate cancer, two important indications where current immunotherapies have failed to demonstrate efficacy," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We look forward to further exploring the broad therapeutic potential of NX-1607 while we advance our lead asset bexobrutideg, an oral BTK degrader, into pivotal trials in patients with relapsed or refractory chronic lymphocytic leukemia."

About NX-1607
NX-1607 is an investigational first-in-class oral inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) being developed for immuno-oncology indications, including a range of solid tumor types. CBL-B is a cytoplasmic E3 ubiquitin ligase that negatively regulates T cell activation, making it an attractive target for immuno-oncology and offering a novel therapeutic approach to treat solid tumors. Inhibition of CBL-B in preclinical studies reverses T cell exhaustion, alleviates tumor-induced immunosuppression, and may also exert direct antitumor effects. Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in the Phase 1a portion. Additional information on the NX-1607 clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).

(Press release, Nurix Therapeutics, OCT 18, 2025, View Source [SID1234656775])

On October 18, 2025 NuCana plc (NASDAQ: NCNA) ("NuCana" or the "Company") reported data at the European Society for Medical Oncology Congress 2025 ("ESMO") on a new model system investigating the synergistic effects of NUC-7738 and PD-1 inhibition in primary organoids derived from patients with renal cell carcinoma ("RCC").

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Using patient-derived organoids ("PDOs") from ten patients with RCC and autologous tumor-infiltrating lymphocytes ("TILs"), co-culture experiments reveal that NUC-7738 enhances the effectiveness of PD-1 inhibitors, resulting in increased tumor cell killing. This combinatorial approach may offer a new option for cancers that no longer respond to anti-PD-1 therapy by targeting multiple aspects of the tumor microenvironment through the disruption of RNA polyadenylation and subsequent changes in cancer cell gene expression.

The data presented at ESMO (Free ESMO Whitepaper) reinforces the mechanism of action for NUC-7738 as observed in the ongoing Phase 1/2 NuTide:701 clinical study. Data to date from NuTide:701 have demonstrated a favorable safety profile, meaningful tumor volume reduction, and prolonged progression-free survival in patients with PD-1 inhibitor refractory and resistant metastatic melanoma.

Andrew Kay, NuCana’s Executive Chairman said: "We are excited to share these new data on NUC-7738 in combination with PD-1 inhibitors in a real-time organoid model system. In addition to demonstrating clear benefits of combining PD-1 inhibitors with NUC-7738, similar to those seen in patients on the ongoing NuTide:701 study, this may lead to robust, patient-specific testing for a selection of immune checkpoint therapies."

Mr. Kay continued: "The translational data that has been generated in this study increases our confidence that the effects we are seeing are a result of NUC-7738 targeting multiple aspects of the tumor microenvironment and increasing PD-1 inhibition. Our data on mechanism of action of NUC-7738 indicate that the phenomena are not restricted to a single tumor type, and that NUC-7738 may have the ability to sensitize many cancers to PD-1 inhibitor therapy."

Based on the exciting initial data from the Phase 1/2 NuTide:701 clinical study, regulators have approved the expansion of the study to recruit an additional 28 patients with PD-1 inhibitor-resistant melanoma. NuCana is currently recruiting patients to this expansion study and plans to meet with the U.S. Food and Drug Administration to discuss the data from this study to determine the optimal registration strategy to support marketing approval.

The details of NuCana’s presentation at ESMO (Free ESMO Whitepaper) are as follows:

Abstract Title: Patient Derived Organoids Reveal Synergy Between NUC-7738 and PD-1 Inhibition in Renal Cell Cancer
Poster Number: 1530P
Session: Investigational Immunotherapy
Date: Sunday, October 19, 2025
Presenting Author: H. Abdullah

(Press release, Nucana, OCT 18, 2025, View Source [SID1234656774])